Journal
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
Volume 98, Issue -, Pages 26-33Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.semcdb.2019.05.031
Keywords
alpha-Ketoglutarate; Tumor progression; Hypoxia; Epigenetics; Cancer metabolism; Drosophila melanogaster
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Funding
- EU H2020 ITN Marie Curie project TRANSMIT [GA722605]
- Associazione Italiana Ricerca sul Cancro (AIRC) grant TOUCH ME [IG17387]
- University of Bologna AlmaIdea Junior grant INTACT
- Italian Ministry of Health grant DISCO TRIP [GR-2013-02356666]
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The thriving field that constitutes cancer metabolism has unveiled some groundbreaking facts over the past two decades, at the heart of which is the TCA cycle and its intermediates. As such and besides its metabolic role, alpha-ketoglutarate was shown to withstand a wide range of physiological reactions from protection against oxidative stress, collagen and bone maintenance to development and immunity. Most importantly, it constitutes the rate-limiting substrate of 2-oxoglutarate-dependent dioxygenases family enzymes, which are involved in hypoxia sensing and in the shaping of cellular epigenetic landscape, two major drivers of oncogenic transformation. Based on literature reports, we hereby review the benefits of this metabolite as a possible novel adjuvant therapeutic opportunity to target tumor progression. This article is part of the special issue Mitochondrial metabolic alterations in cancer cells and related therapeutic targets.
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